Triethylamine → Ethyl (S)-1-cyclopropyl-7-(3-(N,N-dibenzylaminomethyl)-3-fluoromethylpyrrolidin-1-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate

HRID 1489173Notes

Reaction equation

HRID 1489173 reaction equation
Cl.[CH2:2]([N:9]([CH2:17][C@@:18]1([CH2:35][F:36])[CH2:22][CH2:21][N:20]([C:23]2[C:31]([F:32])=[CH:30][C:26]([C:27](Cl)=[O:28])=[C:25](F)[C:24]=2[F:34])[CH2:19]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CN([C:40](=[CH2:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42])C.C(N(CC)CC)C.[CH:54]1([NH2:57])[CH2:56][CH2:55]1>C(#N)C>[CH:54]1([N:57]2[C:25]3[C:26](=[CH:30][C:31]([F:32])=[C:23]([N:20]4[CH2:21][CH2:22][C@@:18]([CH2:17][N:9]([CH2:10][C:11]5[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=5)[CH2:2][C:3]5[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=5)([CH2:35][F:36])[CH2:19]4)[C:24]=3[F:34])[C:27](=[O:28])[C:40]([C:41]([O:43][CH2:44][CH3:45])=[O:42])=[CH:46]2)[CH2:56][CH2:55]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 69828CyclopropylamineHCID 10103284HCID 10103284, compoundHCID 86751386HCID 86751386, compound

Product 1

HCID 54188444Ethyl (S)-1-cyclopropyl-7-(3-(N,N-dibenzylaminomethyl)-3-fluoromethylpyrrolidin-1-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

(S)-4-(3-(N,N-Dibenzylaminomethyl)-3-fluoromethylpyrrolidin-1-yl)-2,3,5-trifluorobenzoyl chloride hydrochloride (0.97 g) was dissolved in acetonitrile (8 ml). Ethyl N,N-dimethylaminoacrylate (0.27 g) and triethylamine (0.4 g) were dissolved in acetonitrile (1 ml) and dropwise added thereto with stirring at room temperature. The mixture was stirred at room temperature for 1 hour and at 50° C. for 4 hours. The reaction mixture was cooled to room temperature and cyclopropylamine (0.11 g) was added. The mixture was stirred at room temperature for 3 hours and the reaction mixture was concentrated. Water was added to the residue and the mixture was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. Dry dimethylformamide (3 ml) and potassium carbonate (0.26 g) were added to the residue, and the mixture was stirred at 60° C. for 8 hours. Water was added and the mixture was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The obtained oil was purified by silica gel column chromatography (developing solvent; chloroform:methanol=30:1) to give the object compound as a pale-yellow oil.

Workup

  1. additiondropwise added
  2. stirringThe mixture was stirred at room temperature for 1 hour and at 50° C. for 4 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. stirringThe mixture was stirred at room temperature for 3 hours
  5. concentrationthe reaction mixture was concentrated
  6. additionWater was added to the residue
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe extract was washed with water
  9. customdried
  10. concentrationconcentrated
  11. additionDry dimethylformamide (3 ml) and potassium carbonate (0.26 g) were added to the residue
  12. stirringthe mixture was stirred at 60° C. for 8 hours
  13. additionWater was added
  14. extractionthe mixture was extracted with ethyl acetate
  15. washThe extract was washed with water
  16. customdried
  17. concentrationconcentrated
  18. customThe obtained oil was purified by silica gel column chromatography (developing solvent; chloroform:methanol=30:1)

Sources & evidence

ORD record
ord-49b96e4469b649c2940143515f8b210b
Source dataset
uspto-grants-1997_10
Patent number
US05677316

Reaction notes

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